The present invention relates to apparatus and methods for controlled heating of body tissues by high intensity focused ultrasound, commonly referred to by the acronym HIFU.
Elevated temperature treatments are used for a variety of purposes in medical and veterinary practice. In HIFU treatment, ultrasonic energy is focused to a small spot within the body so as to heat the tissues to a temperature sufficient to create a desired therapeutic effect. This technique can be used to selectively destroy unwanted tissue within the body. For example, tumors or other unwanted tissues can be destroyed by applying focused ultrasonic energy so as to heat tissue to a temperature sufficient to kill the tissue, commonly about 60xc2x0 to about 80xc2x0 C., without destroying adjacent normal tissues. Other elevated-temperature treatments include selectively heating tissues so as to selectively activate a drug or to promote some other physiological change in a selected portion of the subject""s body. The term xe2x80x9cheatingxe2x80x9d is used herein as referring to all of these treatments, whereas the term xe2x80x9cablationxe2x80x9d as used herein as specifically referring to procedures in which tissue is deliberately killed.
As disclosed in International Application PCT/US98/1062, published as International Publication WO/98/52465 the disclosure which is hereby incorporated by reference herein, HIFU heating typically is conducted using an ultrasonic emitter having an array of transducers. The transducers are actuated with a drive signal so as to emit therapeutic ultrasonic waves at a selected frequency. Differences in phase can be applied to the drive signal sent to each transducer so that the therapeutic ultrasonic waves tend to reinforce one another constructively at the focal location. As also disclosed in the ""465 publication, the transducer array may be incorporated in a disposable device. As described, for example in copending, commonly assigned U.S. patent applications Ser. No. 09/496,988, filed Feb. 2, 2000 and 60/125,676, filed Mar. 22, 1999, the disclosures of which are also incorporated by reference herein, HIFU. may be applied but transducer arrays which are mounted on a probe such as a catheter which can be introduced into the body as, for example, within the vascular system or into a cavernous internal organ.
Application of intense ultrasonic energy to body tissues can result in a phenomenon referred to as xe2x80x9ccavitationxe2x80x9d in which small bubbles form and collapse. The occurrence of cavitation at any point within the body is dependent upon factors including the local temperature at that point, the composition of the tissue at that point and the characteristics of the ultrasonic energy applied to that point. In some medical procedures, cavitation is regarded as a desirable phenomenon for inducing tissue damage or for breaking up objects such as deposits within the body. However, in typical heating treatments, cavitation is regarded as highly undesirable because it can cause unwanted and unpredictable forms of tissue damage.
Various approaches have been proposed for monitoring cavitation in medical treatments of various types. Cavitation is accompanied by a wide band ultrasonic noise emissions from the region where cavitation is occurring. Vykhodtseva et al., Histologic Effects of High Intensity Focused Ultrasound Exposure with Subharmonic Emission in Rabbit Brain in vivo, Ultrasound in Med. and Biol. Vol. 21, No. 7, pp. 969-979, 1995, employs a hydrophone to monitor ultrasonic noise emission from the brain of rabbit during experimental application of ultrasound. The hydrophone is connected through a filter to an oscilloscope so that the ultrasonic noise emitted at the focal region can be displayed and observed. Grandia et al., U.S. Pat. No. 5,827,204 discloses a system in which cavitation is deliberately produced, and uses a hydrophone for detecting emitted noise with feedback control of the ultrasonic transmitter for the purpose of optimizing cavitation.
Cavitation is also accompanied by an increase in the tendency of the tissue where cavitation occurs to reflect ultrasonic waves as echoes, commonly referred to as xe2x80x9cechogenicityxe2x80x9d. That is, tissues with the bubbles produced in cavitation tend to reflect more ultrasound than the same tissues without such bubbles. Fujimoto et al., U.S. Pat. No. 5,694,936, discloses a system using a separate ultrasonic emitting transducer array for acquiring ultrasonic images of tissues during heating by directing a separate ultrasonic beam through the subject body and monitoring the reflected ultrasound. Areas where cavitation occurs appear as distinct features in such image. The image generated during the therapy is compared to an image taken prior to therapy wherein cavitation is present. If such comparison indicates a difference above a threshold level, the frequency or phase of the therapeutic ultrasonic waves used to produce the heating effect are altered so as to suppress cavitation.
Holland et al., In Vitro Detection of Cavitation Induced by a Diagnostic Ultrasound System, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Volume 39, No. 1, pp. 95-101, January, 1992, discloses monitoring of cavitation induced by a diagnostic ultrasound scanner using a separate ultrasonic scanner.
Fry et al., Ultrasound and Microbubbles: Their Generation, Detection and Potential Utilization in Tissue and Organ Therapyxe2x80x94Experimental, Ultrasound in Medicine and Biology, Vol. 21,. No. 9, pp. 1227-1237, 1995, conducts experimental procedures in tissues such as the brain and prostrate of experimental animals. A transrectal probe for producing lesions in the prostate is used to apply ultrasonic energy and also used to acquire ultrasonic images after each individual site exposure. The reference notes that cavitation can be induced xe2x80x9cwith potential therapeutic possibilities and benefits,xe2x80x9d but that in certain circumstances the system can be operated in the intensity range which produces thermal lesions without cavitation.
Jing et al, U.S. Pat. No. 5,657,760 teaches the use of an ultrasonic technique for monitoring vaporization of tissue during heating induced by a laser beam so to provide feedback control of the laser beam. The reference suggests broadly that the laser used to provide heating can be replaced by other thermal therapy devices such as electromagnetic devices or ultrasound devices.
Despite all of the effects in the art however, further improvement would be desirable. For example, it would be desirable to provide improved methods and apparatus which can minimize the occurrence of cavitation in HIFU procedures, particularly in HIFU procedures using disposable ultrasonic transducers, and to provide such apparatus and methods in a form suitable for use with small ultrasonic transducer arrays suitable for introduction into small spaces within the body.
One aspect of the invention provides methods of applying and controlling high intensity focused ultrasound heating within the body of a living subject such as a human or non-human mammal. Methods according to this aspect of the invention desirably include the steps of applying drive signals to a first set of one or more transducers in an array of transducers to thereby cause said first set of transducers to emit therapeutic ultrasonic waves focused at a focal location and thereby heat tissue at such focal location, and acquiring received signals generated by a second set of one or more transducers in said array responsive to ultrasonic waves impinging on said transducers of second set. The received signals can be summed or otherwise processed to provide a detected signal representing ultrasonic waves reflected or emanating from said focal location. Most preferably, one or more of the transducers included in the first or transmitting set for least some part of the drive signal applying step is also included in the second or receiving set during at least some part of the received signal acquiring step. The method according to this aspect of the invention most preferably also includes the steps of producing a feedback signal based on the detected signal indicating whether cavitation has occurred or is likely to occur at within the subject, such as at the focal location, and altering or terminating the emitted therapeutic ultrasonic waves in response to that feedback signal.
The feedback control provided according to this aspect of the invention limits or eliminates the effect of cavitation. This enhanced safety can be used to provide a greater margin of safety for the patient; to allow application of the therapeutic ultrasonic waves at relatively high power closer to the cavitation threshold and thereby provide more effective heating of the tissue, or both. Moreover, because some or all of the same transducers used to emit the therapeutic ultrasonic waves are also used to detect cavitation, there is no need for additional ultrasonic detectors or other elements mounted at the transducer array. This simplifies construction of the transducer array and makes the transducer array more compact. These advantages are particularly useful where the transducer array is disposable or where the transducer array is inserted into the body of the subject.
The selection of transducers included in the first and second sets can be varied during operation so that different transducers are included in the first and second sets at different times during operation. The detected signal can be provided in response to components of the received signals in a detection band of frequencies outside of the drive frequency band.
The method may further include the step of applying monitoring signals in the detection band to at least some of the transducers to produce emitted monitoring ultrasonic waves so that said detected signal represents an echo of the emitted monitoring ultrasonic waves from the focal location. Alternatively, the drive signals can be applied during drive intervals and suspended during one or more receive intervals interspersed with the drive intervals so that application of the therapeutic ultrasonic waves ceases when a sensing interval begins, and the receive signals can be acquired during the receive intervals. A detected signal acquired during each receive interval may represent an echo of the therapeutic ultrasonic waves applied during the immediately preceding drive intervals reflected from said focal location. In a further alternative, the detected signal may represents noise produced by the patient""s body. The echoes or noise will increase substantially in amplitude when cavitation occurs. Therefore, the detected signal representing such echoes or noise can be compared to a threshold and the feedback signal indicating cavitation can be issued whenever the amplitude of the detected signal exceeds the threshold.
A method of applying and controlling high intensity focused ultrasound heating according to a further aspect of the invention includes the steps of emitting therapeutic ultrasonic waves so that said emitted waves are focused at a focal location within the body of a subject; providing a detected signal representing ultrasonic waves reflected or emanating from the focal location; and producing a feedback signal based on the detected signal indicating whether cavitation has occurred or is likely to occur at said focal location, and moving the focal location relative to the body of the subject in response to the feedback signal. In preferred methods according to this aspect of the invention, the therapeutic ultrasonic waves are altered by redirecting them to a different focal location when the feedback signal indicates cavitation, rather than reduced in power or terminated. For example, heating of a lesion larger than the focal spot size of the system typically requires movement of the focal location so that various locations within the lesion are heated in sequence. In preferred methods according to this aspect of the invention, one location is heated for a selected time, but if cavitation occurs prior to that time, another location is heated for a time sufficient to allow cavitation to subside at the first location. At or after that time, the therapeutic ultrasound waves can be redirected to the first location. The treatment is not interrupted, and the time required to treat the entire lesion is not appreciably increased by the steps required to suppress cavitation.
Methods of applying and controlling ultrasound to a subject according to a further aspect of the invention desirably include the step of positioning an array of transducers adjacent the body of a subject, as, for example, within the body or on the skin, and coupling the transducers to the body of the subject at an interface. For example, where the transducers are disposed outside of the body, the transducers can be coupled to the body using a conventional fluid-filled bag and sound-transmissive gel to provide a low-reflectivity interface. The method according to this aspect of the invention desirably further includes the steps of actuating one or more of the transducers to emit monitoring ultrasonic waves, detecting echoes of said monitoring ultrasonic waves and generating a feedback signal if said detected echoes include echoes having more than a preselected magnitude and a return time less than a preselected minimum return time less than the return time for echoes reflected from a desired focal location within the subject""s body. In this case, the detected echoes indicate sound-reflective obstacles adjacent said one or more of said transducers. The method desirably also includes the step of operating at least some of said transducers to emit therapeutic ultrasonic waves focused at said desired focal location to thereby heat tissue of the subject at such focal location, at a time after application of the monitoring ultrasonic waves and acquisition of the receive signals.
Methods according to this aspect of the invention most preferably further include the step of automatically disabling one or more of the transducers in response to the feedback signal, or generating a human-perceptible alarm signal in response to the feedback signal, or both. The entire treatment can be terminated in response to the feedback signal before the high-powered therapeutic ultrasonic waves are applied or modified to exclude use of a particular transducer which causes a strong echo. Thus, the adverse effects caused by bubbles or other obstacles can be avoided.
Further aspects of the invention provide apparatus capable of carrying out these methods and related methods. Apparatus according to one aspect of the invention includes an ultrasonic emitter including an array of ultrasonic transducers and also includes a drive circuit and sensing circuit connected to said transducers for applying drive signals, monitoring signals or both to transducers in the array as discussed above, for acquiring receive signals from transducers in the array and for providing a detected signal in response to the receive signals representing ultrasonic waves reflected or emanating from the patient""s body. Desirably, the drive and sensing circuit operates the transducers so that least some of the same transducers serve as elements of a first set of transducers used to apply the therapeutic ultrasonic waves and also serve, at the same time or at a different time, in a second set of transducers used to acquire the receive signal.
The apparatus desirably includes a feedback control circuit responsive to the detected signal for producing a feedback signal indicating whether cavitation has occurred or is likely to occur at said focal location and adjusting the drive and sensing circuit so as to alter or terminate the therapeutic ultrasonic waves in response to the feedback signal.
The transducer array may be part of a disposable ultrasonic emitter for intrabody or extracorporeal use. Preferably, the drive and sensing circuit and the feedback control circuits are provided as elements of a reusable actuating unit having a connector adapted to connect the actuating unit to the disposable emitter. A further aspect of the invention provides the actuating unit as a separate entity.